X-ray phase-contrast imaging promises to have a major impact on diagnostic radiology, and has reached the point of feasibility for routine clinical use. Because X-ray phase-contrast imaging utilizes a contrast mechanism based on the refractive index values of tissue, it can permit visualization of object features that present little or no absorption contrast. Consequently, phase-contrast mammography can operate effectively at higher X-ray energies than conventional mammography, resulting in a dramatic reduction of the radiation dose, and potentially the ability to improve imaging of dense breasts. The broad objective of this proposal is to develop and evaluate novel system and algorithm designs for phase-contrast mammography. Our research methodology is designed to bring the distinctive features of phase-contrast imaging a step closer to clinical reality. We will investigate the use of a tungsten anode with relatively high kVp values for low-dose phase- contrast mammography. The geometry of the imaging system will be systematically optimized in conjunction with the X-ray source size and spectrum. We will also implement and evaluate non-conventional imaging systems that employ polycapillary optics to collimate the incident X-ray beam, thereby achieving improved beam-coherence properties and decreased image-acquisition times. Finally, robust numerical algorithms will be developed and implemented for reconstructing images that depict the absorption and refractive properties of breast tissue. Experimental studies will be conducted to verify the imaging models that underlie our computer-simulation studies. Task-based measures of image quality derived from numerical observers and human reader studies will guide our optimization studies and ensure that we arrive at clinically meaningful, optimized solutions. Based on the results of our optimization studies, pre-clinical prototype imagers will be constructed and experimentally investigated. Reader studies will be conducted to assess improvement in image quality as compared to standard radiography and establish the groundwork for future clinical translation of the developed imaging technologies. The specific aims of the project are: (1) To identify optimal imaging geometries and X-ray source properties for X-ray phase-contrast mammography; (2) To investigate the use of polycapillary optics to improve phase-contrast and reduce image acquisition times; (3) To develop and investigate robust methods for quantitative phase-retrieval; (4) To objectively assess image quality produced by the phase-contrast mammography system designs; and (5) To construct and experimentally evaluate prototype phase-contrast mammography imagers. PUBLIC HEALTH RELEVANCE: The development of phase-contrast mammography will yield a powerful and effective new modality for breast cancer imaging. The images it produces will improve a reader's ability to detect subtle cancer features and it could also dramatically reduce the radiation exposure to the patient.